Final Diagnosis -- Low-grade myofibroblastic sarcoma (LGM)

DIAGNOSIS

Low-grade myofibroblastic sarcoma (LGM).

DISCUSSION

LGM is a recently defined malignant mesenchymal/soft-tissue tumor that shows myofibroblastic differentiation (7). The diagnosis of myofibroblastic tumors is difficult due to their rarity and the uncertainties in identifying the myofibroblast (2). The attributes of a myofibroblast place it midway between a smooth muscle cell and a fibroblast with defining ultrastructural markers of both cell types, i.e., the myofilaments and fibronectin fibrils (1, 3). Myofibroblast is not a constituent of normal untraumatized tissues but rather predominates under conditions of trauma (wound-healing) or abnormality (inflammatory and reactive conditions) (2). Myofibroblastic lesions fall into two categories: benign tumors or tumor-like lesions of myofibroblasts, and malignant myofibroblastic sarcomas including LGM (2, 3).

LGM is a rarely encountered pathology and less than 100 cases have been described (2). It occurs most commonly in the head and neck region, including the oral cavity, pharynx and parapharyngeal regions, proximal extremities and trunk, with occasional cases in the abdomen or pelvis (2). Notably, few intracranial LGMs have ever been documented in the literature, with only one report early in 1988 where a primary intracerebral sarcoma was supposed to originate from mesenchymal stem cells undergoing myofibroblastic differentiation(5). The microscopic examination and ultrastructural findings described in the case were quite similar to ours, but LGM was not a diagnostic entity at that time.

The relationship of the previous cerebral trauma and surgery (as well as the sliver clips) to the LGM in this case is speculative, but intriguing since myofibroblastic lesions are associated with reactive and reparative conditions. The question of the cells of origin of this tumor is also interesting. Myofibroblasts have long been thought to derive from local resident mesenchymal cells, particularly fibroblasts, and perhaps less commonly smooth muscle cells, pericytes and/or endothelial cells. However, more recently, recruitment from bone-marrow-derived circulating fibrocytes and epithelial-to-mesenchymal transformation have also been proposed as mechanisms explaining the cellular origin of myofibroblasts (2). In this case, the affected vessels bearing the silver clips and bone-marrow-derived cells migrating to the inflammatory field could be the potential origin of tumor transformation.

It is tempting to speculate that the silver clips in the case had a causative role in the tumorigenesis. However, silver as a carcinogen is not well documented in the literature. The silver clip developed by Cushing in early 20th century has greatly facilitated intraoperative blood control in the early evolution of neurological surgery (8). Nowadays, it's still occasionally used for controlling bleedings from large vessels that otherwise can not be safely coagulated. Subcutaneous implantation of silver foil has been reported to induce formation of fibrosarcomas (6), whereas intramuscular injection of silver powders failed to prove the carcinogenesis (4). Interestingly, it is noticed that the physical form of materials could influence their carcinogenic activity (6), and the discrepancy in the silver as carcinogen might be explained by the physical difference between the foils and powders. Our case strongly suggested the burden of silver clips on cerebral vessels could be potentially carcinogenic, albeit the inflammatory response after local surgery could have also played an adjuvant role in the early phase. The carcinogenic activity may stem from the interaction with the sulfur or amino radicals of proteins, or alternatively the local toxic effects of silver (6).

Although silver clips have not been documented in other myofibroblastic tumors, this case illustrates that such associations should be sought for.

Acknowledgments This work was supported by the National Natural Science Foundation of China (No. 30801177).